Synthesis of the (1→6)-linked thiodisaccharide of galactofuranose: inhibitory activity against a ß-galactofuranosidase.

A new (1→6)-linked thiodisaccharide formed by two galactofuranosyl units has been synthesized. Methyl (methyl α,ß-D-galactofuranosid)uronate was employed as the starting compound, which was per-O-silylated with TBSCl and reduced with LiAlH4 to afford methyl 2,3,5-tri-O-tert-butyldimethylsilyl-ß-D-galactofuranoside (2ß) as a key precursor for the preparation of methyl per-O-tert-butyldimethylsilyl-6-thio-ß-D-galactofuranoside (12). The free thiol group of 12 was glycosylated and the product O-deprotected to afford the target ß-D-Galf-S-(1→6)-ß-d-Galf-OMe (14). The conformations of this thiodisaccharide were preliminarily studied using combined theoretical calculations and NMR data. Furthermore, the glycomimetic 14 showed to be a competitive inhibitor of the ß-galactofuranosidase from Penicillum fellutanum (K(i)=3.62 mM).